Tratamiento del cáncer de próstata con radioterapia externa : factores pronóstico /

Títol obtingut de la portada digitalitzadaConsultable des del TDXEl cáncer de próstata es el más frecuente en el varón y la tercera causa de muerte por cáncer en España. Su historia natural es incierta. La prostatectomía radical sigue siendo el tratamiento de elección en los estadios localizados. La radioterapia es un tratamiento curativo alternativo a la prostatectomía radical y el tratamiento de elección en los tumores localmente avanzados. El mejor conocimiento de los factores pronóstico permite individualizar y optimizar los tratamientos con radioterapia. Pacientes y Método: Se han revisado 981 paciente con cáncer de próstata localizado tratados con radioterapia externa con intención radical en el Hospital de la Santa Creu i Sant Pau entre 1979-1999. Edad media: 68.5 años. Estadio: 24% T1, 45% T2, 29% T3, 1% T4 y 1% N+. En 12% Gleason desconocido, 13% ≤ 4, 60% ≤ 7 y 15% > 7. Un 17% de los pacientes sin PSA inicial, 4% 10-20 ng/ml y 23% > 20 ng/ml. Grupo de riesgo: 20% bajo, 28% intermedio, 27% alto y 25% no clasificables. Un 58% realizó hormonoterapia. 30% de los pacientes se trataron con cobaltoterapia y 70% con fotones de 18 MV. Dosis media próstata: 70 Gy. En 673 pacientes se ha valorado el control bioquímico según la definición propuesta por ASTRO. Para la valoración de la toxicidad se han utilizado las escalas de la RTOG. Resultados: *Respuesta a la radioterapia: 18% no respondieron a la radioterapia. Existe una diferencia estadísticamente significativa entre el valor medio del PSA nadir del grupo de pacientes que presentaron fallo bioquímico y el del grupo sin fallo bioquímico (1.12 vs 0.65 ng/ml; p 7. PSA values: 17% unknown, 4% 10-20 ng/ml and 23% > 20 ng/ml. Risk groups: 20% low risk, 28 % intermediate risk, 27% high risk and 25% were unclassifiable. Fifty-eight percent of patients received concomitant androgen suppression. Cobalt therapy was used in 30% of patients and 18 MV X-rays in 70%. The mean dose delivered was 70 Gy. Biochemical control was calculated according to the ASTRO definition in 673 patients. RTOG score was used to assess toxicity. Results: *Radiation response: 18% were non-responders. The mean nadir PSA (nPSA) was 1.12 ng/ml for biochemical failure-free survival (BFFS) patients and 0.65 ng/ml for the group with BF (p< 0.001). A nPSA ≥ 1 ng/ml was related to greater probability of BF (p= 0.013), cancer progression (p=0.001) and prostate cancer death (p=0.001). Taking longer than 1 year to reach nPSA (TnPSA) was associated with less biochemical and/or clinical progression (24% vs 41%; p 0 0.001). *Biochemical failure: 27%; Prognostic factors: age (p=0.010), stage (p=0.001), Gleason (p=0.003), nadir PSA < 1 ng/ml (p=0.033). 39% of patients with BF showed clinical progression compared to 8% in the BFFS group (p< 0.001). *Local relapse: 10.4%; Prognostic factors: stage (p=0.005) and dose (p= 0.005). *Metastases: 11%; prognostic factors: age (p=0.046), Gleason (p=0.006), stage (p=< 0.001), dose (p=0.009), nPSA < 1 ng/ml (p< 0.001), BF (p<0.001) and local relapse (p=0.009). *Acute toxicity grade ≥ 2: 66%. The use of cobalt energy (p= 0.014) and pelvic irradiation (p=0.019) was significantly associated with acute complications. *Late toxicity: grade ≥ 2: 22.8%. Prognostic factors: acute toxicity (p<0.001), previous transurethral resection of prostate (TURP) (p=0.009) and pelvic irradiation (0.041). *Overall survival: 84%, 51% and 38% at 5, 10 and 15 years, respectively. *Cause-specific survival: 93%, 68% and 57% at 5, 10 and 15 years respectively. Stage was the most powerful factor associated to prostate cancer death followed by the radiation dose and nadir PSA. *BFFS: 72.6% at both 5 and 10 years. *Progression free-survival: 58% and 30% at 5 and 10 years respectively. Prostate cancer represented 50% of all deaths (9% of patients). There was a significant association between stage and prostate cancer death (20% for stages T3-T4 and 3.8% for stages T1-T2). Conclusions: external beam radiation is a curative treatment for localized prostate cancer and toxicity is acceptable. Clinical stage and radiation dose are strong prognostic factors of cancer progression

Dones de Vila-real: dos experiències de visibilització femenina des dels camps de la medicina i la política

Treball Final de Màster Universitari en Investigació Aplicada en Estudis Feministes, de Gènere i Ciutadania (Pla de 2013). Codi: SBH023. Curs: 2014-2015Qüestions com l’atribució de rols i característiques concretes per cadascun dels sexes i, per causa d’això, la discriminació sofrida per les dones pel fet de pertanyer a un gènere determinat, a més de la invisibilització de la constant lluita femenina per establir unes pautes igualitaries, formen part d’un tema que s’ha debatut des de sempre i que es remonta al principi de la historia de la humanitat, estant als nostres dies encara −malauradament− d’actualitat. L’objectiu d’aquest treball de Fi de Màster és presentar una visió de la realitat femenina a les últimes dècades del segle XX, amb els antecedents corresponents, i donar a conèixer com la lluita per la desitjada igualtat s’ha nodrit de xicotetes lluites particulars que han anant sumant esforços i triomfs per aconseguir allò que es creu just. L’eix del treball girarà al voltant dels camps de l’educació, la medicina i la política, per ser aquests els que s’exemplifiquen amb el testimoni de les dos dones de la ciutat de Vila-real sobre les quals hem treballat: Concepción Capella i MªGràcia Molés. Amb aquest enfocament multidisciplinar, s’intentará reflectir de la manera més clara possible i amb la major exactitud, a més del panorama a l’Estat, la situació del País Valencià, i més concretament de Vila-real.The issue of the allocation of roles and characteristics specific to each gender and because of this, the woman sofrida discrimination for belonging to a specific genre, in addition to the invisibility of the constant struggle to establish women egalitarian standards is an issue that has been debated ever since it dates back to the beginning of human history, being the present still topical. The aim of this paper is to present Master Thesis from a global vision of the reality of women in the last decades of the twentieth century, with the corresponding background, and known as the fight for equality is desired has been nourished by small individual who struggles and triumphs joining forces going to get what it thinks just. The focus of the work will focus on the fields of education, medicine and politics, being those who exemplified the testimony of two women in the city of Villarreal on which we worked. This multidisciplinary approach will attempt to reflect as clearly and as accurately as possible, besides the scene to the state, the situation in Valencia, and more specifically of Villarreal

Tratamiento del cáncer de próstata con radioterapia externa: factores pronóstico

El cáncer de próstata es el más frecuente en el varón y la tercera causa de muerte por cáncer en España. Su historia natural es incierta. La prostatectomía radical sigue siendo el tratamiento de elección en los estadios localizados. La radioterapia es un tratamiento curativo alternativo a la prostatectomía radical y el tratamiento de elección en los tumores localmente avanzados. El mejor conocimiento de los factores pronóstico permite individualizar y optimizar los tratamientos con radioterapia.Pacientes y Método: Se han revisado 981 paciente con cáncer de próstata localizado tratados con radioterapia externa con intención radical en el Hospital de la Santa Creu i Sant Pau entre 1979-1999. Edad media: 68.5 años. Estadio: 24% T1, 45% T2, 29% T3, 1% T4 y 1% N+. En 12% Gleason desconocido, 13% &#8804; 4, 60% &#8804; 7 y 15% > 7. Un 17% de los pacientes sin PSA inicial, 4% 10-20 ng/ml y 23% > 20 ng/ml. Grupo de riesgo: 20% bajo, 28% intermedio, 27% alto y 25% no clasificables. Un 58% realizó hormonoterapia. 30% de los pacientes se trataron con cobaltoterapia y 70% con fotones de 18 MV. Dosis media próstata: 70 Gy. En 673 pacientes se ha valorado el control bioquímico según la definición propuesta por ASTRO. Para la valoración de la toxicidad se han utilizado las escalas de la RTOG.Resultados: *Respuesta a la radioterapia: 18% no respondieron a la radioterapia. Existe una diferencia estadísticamente significativa entre el valor medio del PSA nadir del grupo de pacientes que presentaron fallo bioquímico y el del grupo sin fallo bioquímico (1.12 vs 0.65 ng/ml; pConclusión: La radioterapia externa es un tratamiento curativo del cáncer de próstata localizado con una toxicidad aceptable. El estadio clínico y la dosis de radioterapia son factores pronóstico que se asocian fuertemente a la progresión de la enfermedad.Prostate cancer is the most common malignant disease and the third leading cause-related death in men in Spain. Radical prostatectomy is the most common treatment for early prostate cancer. Radiotherapy is a curative alternative for these patients and the appropriate treatment for locally advanced tumors. Prognostic factors play an important role in optimal management of this disease.Patients and Methods: Between 1979 and 1999, 981 men with prostate cancer received potential curative external beam radiotherapy at the Hospital de la Santa Creu i Sant Pau. All clinical records were reviewed. Mean age was 68.5 years (ranging 44-84). Stages were: 24% T1; 45% T2, 29% T3, 1% T4 and 1% N+. Gleason score: 12% unknown, 13% &#8804; 4, 60% 5-7 and 15% > 7. PSA values: 17% unknown, 4% 10-20 ng/ml and 23% > 20 ng/ml. Risk groups: 20% low risk, 28 % intermediate risk, 27% high risk and 25% were unclassifiable. Fifty-eight percent of patients received concomitant androgen suppression. Cobalt therapy was used in 30% of patients and 18 MV X-rays in 70%. The mean dose delivered was 70 Gy. Biochemical control was calculated according to the ASTRO definition in 673 patients. RTOG score was used to assess toxicity.Results: *Radiation response: 18% were non-responders. The mean nadir PSA (nPSA) was 1.12 ng/ml for biochemical failure-free survival (BFFS) patients and 0.65 ng/ml for the group with BF (pConclusions: external beam radiation is a curative treatment for localized prostate cancer and toxicity is acceptable. Clinical stage and radiation dose are strong prognostic factors of cancer progression

Evaluation of mass transfer coefficients in biotrickling filters: experimental determination and comparison to correlations

This is the pre-peer reviewed version of the following article: Dorado, A.D. [et al.]. Evaluation of mass transfer coefficients in biotrickling filters: experimental determination and comparison to correlations. "Chemical engineering and technology", Setembre 2009, vol. 32, núm. 12, p. 1941-1950, which has been published in final form at https://doi.org/10.1002/ceat.200900275. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Overall mass transfer coefficients (KGa and KLa) were determined experimentally for four different-nature packing materials used in gas-phase biotrickling filters. A simple methodology based on overall mass balances and following a standard procedure allowed to calculate the mass transfer coefficients under different operating conditions corresponding to usual biotrickling filtration situations. Results showed an increase of mass transfer resistance when increasing the empty bed residence time (EBRT) of the reactor for all packing materials. Experimental results were fitted to existing and well-accepted correlations used in conventional biofilter or biotrickling filter modeling. The comparison of experimental and theoretical data showed huge discrepancies. Simple correlations for the experimental data obtained in this study were also suggested.Peer ReviewedPostprint (author's final draft

Online oxygen monitoring using integrated inkjet-printed sensors in a liver-on-a-chip system

The demand for real-time monitoring of cell functions and cell conditions has dramatically increased with the emergence of organ-on-a-chip (OOC) systems. However, the incorporation of co-cultures and microfluidic channels in OOC systems increases their biological complexity and therefore makes the analysis and monitoring of analytical parameters inside the device more difficult. In this work, we present an approach to integrate multiple sensors in an extremely thin, porous and delicate membrane inside a liver-on-a-chip device. Specifically, three electrochemical dissolved oxygen (DO) sensors were inkjet-printed along the microfluidic channel allowing local online monitoring of oxygen concentrations. This approach demonstrates the existence of an oxygen gradient up to 17.5% for rat hepatocytes and 32.5% for human hepatocytes along the bottom channel. Such gradients are considered crucial for the appearance of zonation of the liver. Inkjet printing (IJP) was the selected technology as it allows drop on demand material deposition compatible with delicate substrates, as used in this study, which cannot withstand temperatures higher than 130 °C. For the deposition of uniform gold and silver conductive inks on the porous membrane, a primer layer using SU-8 dielectric material was used to seal the porosity of the membrane at defined areas, with the aim of building a uniform sensor device. As a proof-of-concept, experiments with cell cultures of primary human and rat hepatocytes were performed, and oxygen consumption rate was stimulated with carbonyl-cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP), accelerating the basal respiration of 0.23 ± 0.07 nmol s-1/106 cells up to 5.95 ± 0.67 nmol s-1/106 cells s for rat cells and the basal respiration of 0.17 ± 0.10 nmol s-1/106 cells by up to 10.62 ± 1.15 nmol s-1/106 cells for human cells, with higher oxygen consumption of the cells seeded at the outflow zone. These results demonstrate that the approach of printing sensors inside an OOC has tremendous potential because IJP is a feasible technique for the integration of different sensors for evaluating metabolic activity of cells, and overcomes one of the major challenges still remaining on how to tap the full potential of OOC systems.Peer ReviewedPostprint (author's final draft

Association of Polymorphisms in the Interleukin 6 Receptor Complex with Obesity and Hyperandrogenism

10 pages, 5 tables.Objective: Interleukin-6 (IL-6), is an inflammatory cytokine that may influence the pathogenesis of obesity and hyperandrogenism. IL-6 exerts its actions through a heterodimeric receptor consisting of two membrane-bound glycoproteins: an 80-kDa IL-6 binding unit (IL6R-alpha) and a 130-kDa IL-6 signal transducer (gp130). Genetic variability at these loci might contribute to explain the development of obesity and hyperandrogenism. Research Methods and Procedures: We have evaluated the possible association of several polymorphisms in the IL6R-alpha and gp130 genes with obesity and/or hyperandrogenism in a case-control study involving 143 hyperandrogenic patients and 45 healthy women from Spain. Results: A microsatellite CA-repeat polymorphism in the IL6R-alpha locus was associated with obesity. The frequency of the common 149-bp allele was markedly increased in obese women compared with controls when considering patients and controls as a whole (0.41 vs. 0.29, chi2 = 17.085, p < 0.050). On the other hand, the uncommon Arg148 allele of the Gly148Arg polymorphism in the gp130 gene was more frequent in controls compared with hyperandrogenic patients (0.17 vs. 0.08, chi2 = 5.605, p = 0.026). Controls carrying Arg148 alleles had lower 11-deoxycortisol and 17-hydroxyprogesterone concentrations, a lower response of androstenedione to 1–24 adrenocorticotropin, and an almost significant decrease in free testosterone levels, suggesting that Arg148 alleles in the gp130 gene have a protective effect against androgen excess and adrenal hyperactivity. Discussion: Polymorphisms in the gp130 and IL6R-alpha loci influence hyperandrogenism and obesity, respectively. Our present results further suggest that proinflammatory genotypes are involved in the pathogenesis of these common metabolic disorders.This work was supported by grants from the Consejería de Educación, Comunidad de Madrid, Spain (Proyectos 08.6/0022/1998, 08.6/0024.2/2000, and 08.6/0010/2001), and from the Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo, Spain (Proyectos FIS 00/0414 and 02/0741 to H.F.E.-M.Peer reviewe

Palmoplantar epidermoid cysts: two cases and brief review of the literature

Palmoplantar epidermoid cysts can range in clinical presentation from an asymptomatic slowly enlarging mass to a painful nodule. We report two cases: an epidermoid cyst on the sole and another on the palm. This article reviews the possible etiology, diagnosis, and prognosis of palmoplantar epidermoid cysts

ATP crossing the cell plasma membrane generates an ionic current in Xenopus oocytes

The presence of ATP within cells is well established. However, ATP also operates as an intercellular signal via specific purinoceptors. Furthermore, nonsecretory cells can release ATP under certain experimental conditions. To measure ATP release and membrane currents from a single cell simultaneously, we used Xenopus oocytes. We simultaneously recorded membrane currents and luminescence. Here, we show that ATP release can be triggered in Xenopus oocytes by hyperpolarizing pulses. ATP release (3.2 +/- 0.3 pmol/oocyte) generated a slow inward current (2.3 +/- 0.1 microA). During hyperpolarizing pulses, the permeability for ATP(4-) was more than 4000 times higher than that for Cl(-). The sensitivity to GdCl(3) (0. 2 mm) of hyperpolarization-induced ionic current, ATP release and E-ATPase activity suggests their dependence on stretch-activated ion channels. The pharmacological profile of the current inhibition coincides with the inhibition of ecto-ATPase activity. This enzyme is highly conserved among species, and in humans, it has been cloned and characterized as CD39. The translation, in Xenopus oocytes, of human CD39 mRNA encoding enhances the ATP-supported current, indicating that CD39 is directly or indirectly responsible for the electrodiffusion of ATP

Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity

7 pages, 2 tables.-- Results from this work were presented at the 85th Annual Meeting of The Endocrine Society, Philadelphia, PA, June 2003.We have evaluated the possible association of polycystic ovary syndrome (PCOS) with 15 genomic variants previously described to influence insulin resistance, obesity, and/or type 2 diabetes mellitus. Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase (three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-gamma2, protein tyrosine phosphatase 1B (two variants), adiponectin (two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor. Compared with controls, PCOS patients were more frequently homozygous for the -108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). Paraoxonase is a serum antioxidant enzyme and, because -108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. G alleles of the ApaI variant in IGF2 may increase IGF2 expression, and IGF2 stimulates adrenal and ovarian androgen secretion. In conclusion, the paraoxonase -108 C-->T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder.This work was supported by grants from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Spain (FIS 00/0414, 02/0741, and 02/0578 and RGDM G03/212) and from the Consejería de Educación, Comunidad de Madrid, Spain (CAM 08.6/0024/2000 and 08.6/0010/2001).Peer reviewe

Vitamin D and Wnt3A have additive and partially overlapping modulatory effects on gene expression and phenotype in human colon fibroblasts

The Wnt/β-catenin signalling pathway is essential for intestinal epithelium homeostasis, but its aberrant activation is a hallmark of colorectal cancer (CRC). Several studies indicate that the bioactive vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proliferation and promotes epithelial differentiation of colon carcinoma cells in part through antagonism of the Wnt/β-catenin pathway. It is now accepted that stromal fibroblasts are crucial in healthy and pathologic intestine: pericryptal myofibroblasts are constituents of the stem cell niche and cancer-associated fibroblasts (CAFs) contribute to CRC progression. However, studies on the combined action of 1,25(OH)2D3 and Wnt factors in colon fibroblasts are lacking. Here we show by global transcriptomic studies that 1,25(OH)2D3 and Wnt3A have profound, additive, partially overlapping effects on the gene expression profile of CCD-18Co human colon myofibroblasts. Moreover, 1,25(OH)2D3 and Wnt3A inhibit CCD-18Co cell proliferation and migration, while 1,25(OH)2D3 reduces, but Wnt3A increases, their capacity to contract collagen gels (a marker of fibroblast activation). These data were largely confirmed in patient-derived primary colon normal fibroblasts and CAFs, and in fibroblasts from other origins. Our results indicate that 1,25(OH)2D3 and Wnt3A are strong regulators of colon fibroblast biology and contribute to a better knowledge of intestinal homeostasis and stromal fibroblast action in CRCThe work in the authors’ laboratories is supported by the Spanish Ministerio de Ciencia, Innovación y Universidades - Fondo Europeo de Desarrollo Regional (FEDER) (SAF2016-76377-R, SAF2017-90604-REDT), Consejo Superior de Investigaciones Científicas (201820I058), and Instituto de Salud Carlos III - FEDER (CIBERONC, CB16/12/00273; CIBERES, CB15/00037